Influenza vaccine

Abstract

The present invention relates to monovalent influenza vaccine formulations and vaccination regimes for immunising against influenza disease, their use in medicine, in particular their use in augmenting immune responses to various antigens, and to methods of preparation. In particular, the invention relates to monovalent influenza immunogenic compositions comprising an influenza antigen or antigenic preparation thereof from an influenza virus strain being associated with a pandemic outbreak or having the potential to be associated with a pandemic outbreak, in combination with an oil-in-water emulsion adjuvant comprising a metabolisable oil, a sterol and/or a tocopherol such as alpha tocopherol, and an emulsifying agent.

We claim: 
     
       1. A method for protecting a human against influenza virus infection, the method comprising a first step of administering to the human one dose of a first monovalent influenza vaccine composition comprising a low amount of influenza virus antigen or antigenic preparation from an influenza virus H1N1 strain that is associated with a pandemic, or has the potential to be associated with a pandemic, in combination with an adjuvant, wherein the low antigen amount does not exceed 15 μg of HA per dose, and wherein said adjuvant is an oil-in-water emulsion comprising a metabolizable oil, a sterol and/or a tocopherol, and an emulsifying agent, and wherein said vaccine composition induces at least one effect chosen from the group of: (i) an improved CD4 T-cell immune response, as compared to unadjuvanted formulation; (ii) an improved B cell memory response, as compared to unadjuvanted formulation; and (iii) an improved humoral response, as compared to unadjuvanted formulation, against said virus or antigenic composition; and a second step of revaccinating said human by administering a dose of a second monovalent vaccine composition comprising an influenza virus antigen or antigenic preparation thereof from a circulating pandemic H1N1 strain of the same subtype as that used in the first monovalent influenza vaccine composition and that is antigenically different from that used in the first monovalent influenza vaccine composition. 
     
     
       2. The method as claimed in  claim 1 , wherein said CD4 T-cell immune response involves the induction of a cross-reactive CD4 T helper response or the induction of a cross-reactive humoral immune response. 
     
     
       3. The method as claimed in  claim 1 , wherein said immune response or protection meets criteria chosen from the group consisting of: at least one of the three international regulatory criteria for influenza vaccine efficacy, at least two of the three international regulatory criteria for influenza vaccine efficacy, and all three of the international regulatory criteria for influenza vaccine efficacy. 
     
     
       4. The method as claimed in  claim 1 , wherein said vaccine is administered parenterally. 
     
     
       5. The method as claimed in  claim 1 , wherein said HA antigen amount does not exceed 10 μg per dose. 
     
     
       6. The method as claimed in  claim 1 , wherein the second monovalent vaccine composition used for the revaccination contains an adjuvant. 
     
     
       7. The method as claimed in  claim 6 , wherein said adjuvant is an oil-in-water emulsion adjuvant. 
     
     
       8. The method as claimed in  claim 1 , wherein said second monovalent vaccine composition for revaccination contains an influenza virus or antigenic preparation thereof that shares common CD4 T-cell epitopes or common B cell epitopes with the influenza virus or antigenic preparation thereof used for the first monovalent influenza vaccine composition. 
     
     
       9. The method as claimed in  claim 1 , wherein the first monovalent influenza vaccine composition is made with an influenza virus H1N1 strain that could potentially cause a pandemic, and the revaccination with the second monovalent vaccine composition is made with an influenza composition containing a circulating pandemic strain, which is antigenically different from said influenza virus H1N1 strain of the first monovalent influenza vaccine composition and comprises CD4 T-cell epitopes from the first monovalent influenza vaccine composition. 
     
     
       10. The method of  claim 1 , wherein said influenza virus infection in said human is caused by a strain of influenza that is a variant of said H1N1 strain found in said first monovalent influenza vaccine composition. 
     
     
       11. The method as claimed in  claim 10 , wherein the first influenza strain is associated with a pandemic or has the potential to be associated with a pandemic. 
     
     
       12. The method as claimed in  claim 1 , wherein said tocopherol is present in an amount of 1.0% to 20% of the total volume of said first monovalent influenza vaccine composition. 
     
     
       13. The method of  claim 9 , wherein the circulating pandemic strain is a variant of the influenza virus H1N1 strain. 
     
     
       14. The method of  claim 13 , wherein the variant is a drift variant of the influenza virus H1N1 strain. 
     
     
       15. The method of  claim 13 , wherein the variant is a shift variant of the influenza virus H1N1 strain. 
     
     
       16. The method as claimed in  claim 1 , where the second monovalent vaccine composition is administered 1 to 14 months after the first monovalent influenza composition.